The intestinal barrier, disruption, invasion and inflammatory destruction by pathogens

The second lecture, entitled "The intestinal barrier: disruption, invasion and inflammatory destruction by pathogens", was originally intended as a relatively exhaustive review of the various strategies employed by bacteria and viruses to cross, more or less "noisily", the intestinal epithelium and mucosa - so-called entero-invasive pathogens. As some of this topic had already been covered in the 2008-2009 lectures, I decided to refocus this presentation on very recent data demonstrating a much deeper symbiosis between mammals and their intestinal microbiota than previously thought, with the symbiotic process taking place via the translocation of bacteria or bacterial motifs(pathogen-associated molecular pattern or PAMP) such as endotoxin or muropeptides, fragments of peptidoglycan, the bacterial wall. This concept of "physiological bacterial translocation" is proving to play an essential role at local level in the maturation of the vasculature and its immune system, for example, but it also modulates the maturation of the peripheral immune system. In addition, and in a hitherto unappreciated way, this bacterial translocation appears to play a major role in metabolism, particularly in insulin resistance which, if left unregulated, can lead to obesity and diabetes. One of the main mechanisms is the accumulation of bacterial products in the mesenteric lipid mass, causing inflammation which in turn leads to adipocyte dysfunction. We're only at the beginning of observing these unexpected aspects of the human-microbe symbiosis. Indeed, it seems that the presence of a microbiota is essential, for example, in maintaining the level of anti-infectious immune defense mechanisms, and in the late stages of central nervous system maturation, with potentially significant consequences for its functioning and behavior. It is perhaps the decline in the intensity of this symbiosis over the last few decades, as a result of hygiene, vaccination and antibiotics, that has given rise to the emergence of new pathologies, particularly dysimmunity (atopy, asthma, inflammatory bowel disease, etc.). The rational basis of the "hygienist hypothesis" is thus beginning to take shape...